Nakayama K, Watanabe T, Nakagawa T, Kim W S, Nagahama M, Hosaka M, Hatsuzawa K, Kondoh-Hashiba K, Murakami K
Institute of Biological Sciences, University of Tsukuba, Ibaraki, Japan.
J Biol Chem. 1992 Aug 15;267(23):16335-40.
Many peptide hormones and neuropeptides are produced from larger, inactive precursors through endoproteolysis at sites usually marked by paired basic residues (primarily Lys-Arg and Arg-Arg), or occasionally by a monobasic residue (primarily Arg). Based upon data concerning processing of prorenin and its mutants around the native Lys-Arg cleavage site expressed in mouse pituitary AtT-20 cells, we present the following sequence rules that govern mono-arginyl cleavages: (a) a basic residue at the fourth (position -4) or the sixth (position -6) residue upstream of the cleavage site is required, (b) at position -4, Arg is more favorable than Lys, and (c) at position 1, a hydrophobic aliphatic residue is not suitable. These rules are compatible with those proposed by comparison of precursor sequences around mono-arginyl cleavage sites. We also provide evidence that precursor cleavages at mono-arginyl and dibasic sites can be catalyzed by the same Kex2-like processing endoprotease, PC1/PC3.
许多肽类激素和神经肽是由较大的无活性前体通过在通常由成对碱性残基（主要是Lys-Arg和Arg-Arg）标记的位点进行内蛋白水解产生的，偶尔也由单碱性残基（主要是Arg）标记。基于在小鼠垂体AtT-20细胞中表达的肾素原及其突变体在天然Lys-Arg切割位点周围加工的数据，我们提出了以下控制单精氨酸切割的序列规则：(a) 在切割位点上游第四个（-4位）或第六个（-6位）残基处需要一个碱性残基；(b) 在-4位，Arg比Lys更有利；(c) 在1位，疏水性脂肪族残基不合适。这些规则与通过比较单精氨酸切割位点周围前体序列提出的规则一致。我们还提供了证据表明，单精氨酸和双碱性位点的前体切割可以由同一种Kex2样加工内蛋白酶PC1/PC3催化。
